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Abstract
Background: The addition of hydralazine/isosorbide dinitrate (H-ISDN) to a standard heart failure
treatment regimen in the African-American Heart Failure Trial was associated with
a 43% reduction in mortality. However, the effectiveness of H-ISDN in a community
sample of African-American patients and other racial/ethnic groups is unknown.
Objective: The aim of this study was to assess the associations between treatment with H-ISDN
and mortality or hospitalization for heart failure in veterans with the disease.
Methods: For this retrospective cohort study, electronic data on outpatient prescriptions,
comorbidity, and other heart failure risk factors were analyzed in veterans with heart
failure. Patients were classified based on whether they were prescribed H-ISDN and
subclassified based on race/ethnicity (African American, Hispanic, or white). Patients
who were prescribed H-ISDN were subclassified based on time of initiation of H-ISDN
treatment (0–121, 122–365, or >365 days after diagnosis). Data were analyzed using
propensity-adjusted Cox regression analyses, with exposure to H-ISDN modeled as a
time-varying covariate.
Results: Data from 76,828 veterans were analyzed (98% men, 2% women). H-ISDN prescription
was not associated with the risk of death in 5 of the 9 subgroups predefined by race/ethnicity
or time of initiation of H-ISDN; however, H-ISDN was associated with an increased
risk of death in the 4 subgroups with longer times to initiation. H-ISDN was associated
with a significantly increased risk of heart failure hospitalization in all but 1
of the 9 subgroups. The risk of both mortality and hospitalization associated with
H-ISDN was significantly lower in African-American patients than in those who were
Hispanic or white. Concurrent prescription of other, evidence-based heart failure
therapies (eg, angiotensin-converting enzyme inhibitors, β-blockers, and combinations)
had strong, statistically significant associations with reduced mortality.
Conclusions: In this population of veterans with heart failure, H-ISDN prescription was not associated
with significant reductions in mortality or hospitalization in any of the subgroups
defined by race/ethnicity and time of initiation of H-ISDN analyzed compared with
the group that did not receive H-ISDN. It is possible, or even likely, that unmeasured
differences in important risk factors—particularly heart failure severity and left
ventricular dysfunction—between the group that received H-ISDN and the one that did
not masked a beneficial effect of H-ISDN. Therefore, our conclusions must be regarded
as hypothesis generating and need to be tested in subsequent randomized trial(s).
Key words:
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Article info
Publication history
Accepted:
January 26,
2009
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.